MED628 - Neuroinflammation and Diseases of the PNS Flashcards

Question

How does recovery occur in MS?

Answer 1

o Resolution of inflammation o Neuroaxonal redundancy - More nerves than is required o Remyelination occurs  Slow and lags behind clinical recovery  Not always complete o Neuroplasticity

Answer 2

- More severe inflammation? - More demyelination? - More neuroaxonal loss? - More damage elsewhere? - Less remyelination? - Less tissue reserve? (i.e. less redundancy) - Less neuroplasticity?

Answer 3

- Optical coherence tomography (OCT) o A measure of axonal damage - Optic nerve MRI o Gadolinium-enhanced MRI is a measure of inflammation - Diffusion-weighted MRI of the optic radiations o A measure of tract integrity - MRI measurements of cortical thickness and atrophy o A measure of neuroaxonal loss - Functional MRI o A measure of neuroplasticity

Answer 4

- Inflammatory, demyelinating disease - Specific to the central nervous system - Commonest cause of chronic neurological disease in young adults - Usually begins between ages 20-40 years - Early course is relapsing/remitting - Progressive disability over time

Answer 5

- Environment - Genetics - Chance

Answer 6

- Prevalence lower in regions closer to the equator o Prevalence is notably higher in south Australia when compared to the north - More common in females than males o Ratio of 3:1 for early onset o 2:1 for normal range o 2.4:1 for late onset - More common in white males when compared to black and ‘other’ males - Incidence peaks in the 3rd decade of life o Bell shaped curve

Answer 7

- MS prevalence rates can be altered by a change in environment o MS is not a purely genetic disease - Age at migration is critical for risk retention o The potential for developing MS may be established early in life o The younger the age of migration the bigger increase risk of developing MS - But are migrant populations directly comparable to populations in their native country or the population of their adoptive country?

Answer 8

``` o Optic neuritis o Spasticity and other pyramidal signs o Sensory symptoms and signs o Lhermitte’s sign o Nystagmus, double vision and vertigo o Bladder and sexual dysfunction ```

Answer 9

``` o Aphasia o Hemianopia o Extrapyramidal movement disturbance o Severe muscle wasting o Muscle fasciculation ```

Answer 10

``` Cerebral hemispheres Spinal cord Optic nerves Medulla and pons Cerebellar white matter ```

Answer 11

o Large variety of symptoms such as changes to cognition and motor control o Also, many silent lesions

Answer 12

``` o Weakness o Paraplegia o Spasticity o Tingling o Numbness o Lhermitte’s sign – electric shock like sensation beginning in the neck and radiating to trunk and limbs, can be triggered by tilting head forwards o Bladder and sexual dysfunction ```

Answer 13

o Impaired vision | o Eye pain

Answer 14

o Dysarthria o Double vision o Vertigo o Nystagmus

Answer 15

o Dysarthria o Nystagmus o Intention tremor o Ataxia

Answer 16

- Weakness - Paraesthesia - Visual loss - Incoordination - Vertigo - Sphincter impairment

Answer 17

o Clearly defined disease relapses with full recovery or with sequelae and residual deficit upon recovery o Periods between disease relapses characterised by a lack of disease progression

Answer 18

o Disease progression from onset with occasional plateaus and temporary minor improvements allowed

Answer 19

o Initial relapsing-remitting disease course followed by progression with or without occasional relapses, minor remissions and plateaus

Answer 20

o Progressive disease from onset, with clear acute relapses, with or without full recovery with periods between relapses characterised by continuing progression

Answer 21

- Autoimmune disorders such as SLE, Primary Sjogren’s syndrome, Polyarteritis nodosa, ADEM - Infectious diseases such as, Lyme disease, Syphilis, AIDS - Mitochondrial encephalopathy - Arnold-Chiari malformation - Cardiac embolic event

Answer 22

- Less than 5-10% of patients will have a clinically milder phenotype with no significant disability - More than 30% will develop significant disability within 20-25 years after onset - Life expectancy is shortened only slightly - Survival rate linked to disability - Death usually results from secondary complications (pulmonary or renal)

Answer 23

acute and clinically fulminant form of the disease that can lead to coma or death within days

Answer 24

- Male gender - Late age at onset - Early motor, cerebellar, and sphincter symptoms - Short inter-attack interval - High number of early attacks - Early residual disability

Answer 25

- Significant MRI disease burden at onset - Evidence of MRI disease activity - Positive CSF analysis for oligoclonal bands - Positive evoked potential exam

Answer 26

``` - Immunomodulatory therapy for o Acute relapses o Frequent relapses o Aggressive illness o Progressive illness ``` - Management of symptoms - Non-pharmacological treatments o Physiotherapy o Occupational therapy

Answer 27

- Oral or IV methylprednisolone can speed up recovery from a relapse o No evidence that this changes the overall disease progression

Answer 28

Plasmapheresis o The 2011 AAN guidelines for plasmapheresis states that it is ‘probably effective’ as second-line treatment for relapsing MS exacerbations that do not respond to steroids

Answer 29

Disease modifying therapies - Shown beneficial effects in patients with relapsing MS inkling reduced frequency and severity of attacks - Appear to slow progression of disability and reduce accumulation of lesions within the brain and spinal cord

Answer 30

``` o Interferon beta-1a (Avonex, Rebif) o Interferon beta-1b (Betaseron) o Glatiramer (Copaxone) o Natalizumab (Tysabri) o Mitoxantrone (Novantrone) o Fingolimod (Gilenya) ```

Answer 31

- Double-blind, placebo-controlled study of 372 patients with RRMS (comparing no treatment with interferon beta 1b) o Decreased frequency of relapses by 34% after 2 years o In treated patients – MRI T2 lesion burden increased by 3.6% over 5 years, compared to 30.2% in the placebo group o At 5 year follow up – incidence of disease progression was lower in treatment group

Answer 32

Studied the efficacy of intramuscular interferon beta 1a Study of 301 patients o Annual exacerbation rate decreased by 29% o Over 2 years, disease progression occurred in 21.9% in treatment group compared to 34.9% of placebo group o MRI data showed a decrease in mean lesion volume and number of enhancing lesions

Answer 33

- Synthetic polypeptide which probably works by substituting itself as the target for the immune system

Answer 34

- Double-blind trial of 251 patients with RRMS o Resulted in a 29% reduction in relapse rate over 2 years o Accumulation of disability was slowed - Follow up open-label study o Demonstrated efficacy over 6 years

Answer 35

- Humanized monoclonal antibody that binds with the adhesion molecule alpha-4 integrin, inhibiting its adherence to receptors Second line therapy for MS

Answer 36

Placebo-controlled trial | o Reduced relapse rate (68%) and progression of disability (42%) over 2 years

Answer 37

- Associated with progressive multifocal leukocephalopathy (PML)

Answer 38

- First oral disease modifying treatment - Two-year placebo-controlled study o Reduced relapse rates by 54-60%, and reduced disability progression by about 30% - A one-year study showed that it reduced relapse rates by 53% compared to beta interferon 1a

Answer 39

o Transient, generally asymptomatic bradycardia o Atrio-ventricular block with the first dose o Reduction of lymphocyte count can lead to infection o Reversible, asymptomatic elevations of liver enzymes o Headache, diarrhoea, back pain

Answer 40

- High dose cyclophosphamide

Answer 41

That those treated with cyclophosphamide followed by long term maintenance with Glatiramer Acetate – well tolerated and appeared to be effective in reducing risk of relapse, disability progression, and new MRI lesions

Answer 42

o Leukaemia o Lymphoma o Infections o Haemorrhagic cystitis

Answer 43

Mitoxantrone But o Risk of cardiotoxicity increasing with every dose o Risk of leukaemia

Answer 44

- Currently no approved treatments - Previous trials using a number of DMTs o Including interferons, GA, Mitoxantrone, Methotrexate, IVIG, Cyclophosphamide o Show no effect on course of the illness - On-going trial using Fingolimod

Answer 45

Experimental agent for treatment of MS Monoclonal antibody that targets CD52 cells

Answer 46

Three-year phase II trial of 333 patients with early RRMS o 71% reduction in disability progression o 74% reduction in relapse rate

Answer 47

phase III trial comparing Alemtuzumab with Rebif (Interferon beta-1a) in 581 patients o Alemtuzumab showed 55% reduction in relapse rates o No significant difference in disease progression

Answer 48

larger phase III study involving 840 people comparing Alemtuzumab to Rebif o It reduced relapse rates by 49% o Reduced disability progression by 42%

Answer 49

- Dimethyl fumarate | - Oral therapy

Answer 50

2-year phase III placebo-controlled trial of BG12 o Relapse rates reduced by 53% in twice-daily group, 48% in three-times daily o Disability progression reduced by 38% and 34% o MRI scans showed considerable decrease in new or newly enlarging lesions

Answer 51

2-year phase III trial comparing BG-12 with Copaxone (GA) o Relapse rates reduced by 44% (2x daily) and 51% (3x daily) o Disability progression reduced by 21% and 24% o MRI scan showed significant decrease in new or newly enlarging brain lesions

Answer 52

``` o Fatigue o Spasticity o Bladder problems o Bowel problems o Cognitive dysfunction o Pain o Paroxysmal symptoms o Sexual dysfunction o Tremor ```

Answer 53

- Autoreactive lymphocytes become activated in the periphery and migrate to CNS - Form accumulations - Local inflammatory reaction mediated through inflammatory cytokines, complement and cell cytotoxic mechanisms leading to inflammation, axonal injury and demyelination - Patches of inflammation in eloquent areas causes symptoms (e.g. paralysis)

Answer 54

o CD8 T cells o Th17 cells – secrete IL 17 and 22 which disrupts the BBB o B cells o Macrophages

Answer 55

o Conduction block – lack of saltatory conduction o Demyelination – most common pathology, stops neuron from working as ion channels only at nodes of Ranvier o Axonal transection

Answer 56

o Relapse has to be experienced by patient o May be able to be confirmed by examination o Must last >48hrs (rules out other pathology such as seizure or TIA)

Answer 57

o Cerebral hemispheres – cognitive changes, visual field loss, hemiplegia o Optic nerve – visual loss and eye pain (especially on eye movement) o Brainstem – eye movement disorders, vertigo, ataxia, cranial nerve palsies, hemi-, quadriplegias o Spinal cord – weakness, bladder, bowel and sexual difficulties

Answer 58

o Relapsing remitting o Days to weeks onset o Weeks to months recovery o Not always full recovery especially if had MS for a while o Most will lead to secondary progressive

Answer 59

- Periventricular lesions (adjacent to ventricles) – common pattern - Juxtacortical lesions - Callosal lesions and Dawson’s fingers (project outwards on the veins into corpus callosum) - Posterior fossa and brainstem lesions - Temporal lobes lesions - Optic nerve lesions (only seen in good scans) - Spinal cord lesions

Answer 60

An inflammatory demyelinating disease of the CNS where there is: o Dissemination in space o Dissemination in time o No alternative neurologic disease which may explain the symptoms and signs

Answer 61

Organ – pathology o Disease, diagnosis Person – impairment o Observable abnormalities (signs) and subjective experiences (symptoms) Person in environment – disability/activity limitation o Inability to perform an activity o Mobility, communication, activities of daily living Person in society – handicap/participation o Inability to fulfils one’s role

Answer 62

- Any loss or abnormality of psychological, physiological, or anatomical structure or function

Answer 63

- Loss of vision - Dysphagia - Ataxia - Spasticity - Weakness - Incontinence - Pain

Answer 64

- Any restriction or lack of ability to perform an activity in manner or within the range considered as normal Can affect - Walking - Dressing - Washing

Answer 65

- A disadvantage for a given individual resulting from an impairment or disability that limits or prevents the fulfilment of a role that is normal for that individual - Unique to each individual and their personal situation E.g. student may have issues with studying and sport Affects - Family - Society - Vocation

Answer 66

- Identify the problems - Set goals - Decide on the setting - Interventions

Answer 67

Disordered sensori-motor control resulting from an upper motor neuron lesion, presenting as intermittent or sustained involuntary activation of muscles o Pandyan et al, Disability and Rehabil 2005

Answer 68

- Increased tone - Clonus - Spasms - Spastic dystonia - Spastic co-contractions

Answer 69

``` o Posture o Standing o Walking o Transfers o Prevent venous stasis ```

Answer 70

o Pain o Mobility o Seating o Hygiene – hand, genital area

Answer 71

Phsyiotherpay TENS Vibration

Answer 72

Motor neurons o GABA – inhibition – Baclofen o Intrathecal baclofen pump Inhibitory interneurons o Alpha-2 agonist – stimulation of interneurons – Tizanidine o Cannabinoid receptors – Sativex - Neuromuscular junction - Botox - Muscle – Dantrolene (muscle relaxant)

Answer 73

- No response despite use of at least 2 oral anti spasticity drugs in combination - No other causes of spasticity such as pressure ulcers, UTI, calculi, any wounds/infections

Answer 74

o Intrathecal baclofen – delivered directly in the subarachnoid space via silicone catheter through anterior abdominal wall o Phenol – injection o Alcohol – injection o Posterior Rhizotomy – severing spinal nerves in neck

Answer 75

o Serial casting o Splints o Surgery

Answer 76

- Inability to activate ankle dorsiflexors in swing phase of gait - Lesion of central neurological origin – corticospinal tracts

Answer 77

functional electric stimulation (FES)

Answer 78

o Retrospective analysis of 23 MS patients in 2016 o Found both external and implanted devices significantly improved walking speed and walking distance o Indications that walking required less effort o Improved quality of life o (Taylor et al, International Journal of MS Care, 2016)

Answer 79

inhibitory channels o Prevent back propagation of action potentials o Repolarisation

Answer 80

Inhibits potassium channels – better conduction along demyelinated axons o Review published in 2011 o Randomised, double-blind, placebo-controlled trials o Walking speed was improved in 1/3 of patients – was 25% above baseline o (Blight, 2011)

Answer 81

- Detrusor overactivity – frequency, urgency, incontinence - Detrusor areflexia – flaccid, large bladder - Detrusor sphincter dyssynergia – incomplete emptying - Sphincter over activity – retention, hesitancy - Sphincter incompetence – dribbling

Answer 82

- Block parasympathetic nerves - Anticholinergic drugs – oxybutynin, fesoterodine - Block NMJ – Botox - Stimulate sympathetic – Mirabegron – Beta-3 adrenergic receptors - Artificial sphincter

Answer 83

- Tamsulosin – relaxes sphincter | - Catheter

Answer 84

- The recording of electrical activity from muscle - Disposable needle electrode inserted into the muscle - Record from the muscle at the rest - Record motor units following voluntary activation - Specialised techniques – single fibre EMG

Answer 85

o Motor unit analysis o Interference pattern o Spontaneous activity

Answer 86

o Anterior horn cell o Axon o Neuromuscular junction o Muscle fibres

Answer 87

1. Action potential initiated by motor neuron, travels down myelinated axon via saltatory conduction 2. Activation of voltage gated calcium channels, influx of Ca2+, Ach release 3. Ach acts nAchR - influx of Na 4. Muscle membrane potentials: -90mv to -50mv = threshold for voltage-gated sodium channels 5. High influx of sodium – at +20mv, sodium channels become inactivated 6. Increased permeability of the muscle membrane to potassium – K+ leaves, repolarisation of the membrane 7. The AP across the muscle, release of Ca2+ from sarcoplasmic reticulum 8. Ca2+ acts with actin and myosin 9. muscle contraction

Answer 88

- Amplitude – size - Duration - Turns – the number of times it changes directions - Phases – number of times it crosses the baseline

Answer 89

- Electric activity recorded from the muscle during maximal voluntary effort - It is the recruitment of all motor units to the point that no single MUAPs can be distinguished

Answer 90

Look to see if there is a reduced pattern – where there are areas of baseline with no activity despite maximal effort o Lose axons – activate fewer motor units o IP is reduced – you can see gaps in-between the MUAPs

Answer 91

o Fibrillations o Positive sharp waves o Fasciculations o Complex repetitive discharges

Answer 92

Arising from the nerves - could be traumatic, toxic, metabolic, hereditary

Answer 93

- Spontaneous discharge of muscle fibre, always pathological

Answer 94

- Indicate loss of innervation of muscle fibres (e.g. nerve transection) - Deinnervated muscle fibres remain viable but after 7-10 days they become supersensitive - Denervated fibres will have acetylcholine receptors over the entire membrane rather than being concentrated at NMJ

Answer 95

- Spontaneous discharge of part or whole of the motor unit - Longer and more complex than fibrillations - Isolated discharges occurring at irregular intervals - May be visible at the skin if near surface - May be benign or pathological

Answer 96

- Start and stop abruptly - May persist for several minutes - Constant frequency (1-100Hz) - Stereotyped group of single fibre potentials with complex morphology - Probable ephaptic transmission between adjacent muscle fibres - Seen predominantly in neurogenic disease

Answer 97

- Regular or irregular discharge of groups of motor units | - Can be seen as flickering in muscle

Answer 98

Seen in central and peripheral pathology | o Notably – brainstem neoplasms or demyelination and sub clinically in episodic ataxia type 1

Answer 99

1 day – 2 weeks o May still have normal/near normal distal NCS (but EMG likely abnormal) o Poor recruitment on EMG, reduced pattern 3 weeks o Decreased NCS amplitude or absent (Fibrillations on EMG) 4-6 weeks o Nascent potentials on EMG 3 months o Some chronic neurogenic EMG change

Answer 100

Primary muscle pathology Damage to and loss of muscle fibres

Answer 101

- Amplitude – reduced - Duration - <6ms - Phases – increased

Answer 102

- Full and early | - Low amplitude (the MUAPs are low amplitude)

Answer 103

muscle fibre membrane channelopathies

Answer 104

- Recording individual muscle fibres - Used in diagnosis of NMJ transmission disorders - Looking at jitter - Blocking seen with more severe disorder

Answer 105

denervation-reinnervation can also result in immature collateral nerve terminals and instability of neuromuscular transmission seen in (for example ALS)

Answer 106

- Anterior horn cell - Nerve root - Plexus - Peripheral nerve - Neuromuscular junction - (Muscle)

Answer 107

``` o MND o Polio o Radiculopathy o Brachial neuritis o Peripheral neuropathy o Entrapment neuropathy o Myasthenia Gravis o Lambert Eaton Syndrome o Polymyositis o Muscular dystrophy ```

Answer 108

``` Latency Amplitude Area Duration of negative phase Total duration ```

Answer 109

o Median o Ulnar o Peroneal o Tibial

Answer 110

o Median o Ulnar o Radial o Sural

Answer 111

CV = Conduction distance/conduction time

Answer 112

o Arm >48m/s | o Leg >38m/s

Answer 113

- More complex due to the presences of neuromuscular junctions - Need to isolate simply nerve fibres to calculate velocity

Answer 114

Temperature o Conduction velocity decreases with decreasing temperature o Try and warm all patients to 32degrees Averager o Taking multiple recordings to cancel out noise as trace stays constant while noise is random Supramaximal response

Answer 115

Slowed CV Conduction block  Some fibres do not conduct but not all  Reduction in area under curve and amplitude together Dispersion  Reduction in amplitude but area under curve remains the same  Some fibres conduct more slowly due to demyelination which spreads the wave out

Answer 116

o Reduced amplitude (Normal sensory ≥ 5uV) | o Absent potential

Answer 117

- Motor response - Second of the two voltage changes seen in nerve conduction studies - Occurs after supramaximal stimulation of nerve o Stimulation travels in both directions (towards muscle fibre and towards motor cell body) - When stimulus reaches cell body and small proportion backfire and stimulus travels back down the neuron seen as the F wave - Due to a different population of anterior horn cells stimulated every time, each F wave has a different shape, amplitude and latency

Answer 118

Electrical stimulation is delivered to a motor nerve several times a second

Answer 119

- By observing changing in electrical response – can assess for pathology of neuromuscular junction and differentiate between presynaptic and postsynaptic conditions - Most commonly used to diagnose myasthenia gravis

Answer 120

- Somatosensory evoked potentials (upper and lower limb) - Visual evoked potentials (VEP)/ectroretinography (ERG) - Auditory - Motor evoked potential (MEP)

Answer 121

- Responses after electrical stimulation of mixed or cutaneous peripheral nerves - Mixed nerves-electrical stimulation sufficient to produce a visible twitch

Answer 122

o The 10-20 international systems o Electrodes are placed at sites that are 10% or 20% of a measured length from a known landmark on the skull o Same as EEGs

Answer 123

o Slowing CV o Reduced amp or loss of responses o Asymmetries between sides

Answer 124

Suspect demyelination and myelopathy and can help in  Distinguishing central and peripheral process  Prognostication of coma and brainstem death

Answer 125

Asymmetries, prolonged central conduction time, absent responses

Answer 126

markedly prolonged

Answer 127

Giant SSEPs

Answer 128

Continuity of the visual pathways

Answer 129

o Technical error (e.g. electrodes in wrong place) o Poor visual fixation o Severe optic atrophy

Answer 130

slowing of conduction in one optic nerve (optic neuritis)

Answer 131

a conduction defect behind the optic chiasm but | o Specificity and sensitivity not good to confirm posterior lesions

Answer 132

ischaemic and compressive disease of the eye and optic nerve | o Amblyopia and glaucoma

Answer 133

o I – Auditory nerve o II – Cochlear nuclei – lie at rostral pole of medulla o III – Superior olivary complex – in pons o IV – Lateral lemniscus o V – Inferior colliculus – midbrain

Answer 134

o Screening hearing in infants o Evaluation of possible acoustic neuroma o MS o Evaluate peripheral and central auditory pathways in sedated and anaesthetised patients

Answer 135

Diagnostic use – mainly connection between primary motor cortex and various muscles o Pathology from MS, CVA, ALS-PLS o Assess intracortical inhibition etc

Answer 136

- Infection o Bacterial o Viral o Post -viral - Autoimmune o MS o SLE and connective tissue diseases - Ischaemia - Neoplasia

Answer 137

``` Celsus (30 BC to 38 AD) o Calor – heat o Rubor – redness o Dolor – pain o Tumor – swelling ``` Galen (130-200 AD) o Functio laesa – loss of function

Answer 138

- Vascular changes in inflammation - BBB - Consequent changes in tissue water content o T2 signal, DWI

Answer 139

- Increased flow - Increased permeability – the BBB - Increased inflammatory cell adhesion and recruitment

Answer 140

o Can be measure by perfusion imaging ``` o MR perfusion  Contrast enhanced  Arterial spin labelling  Indirect: BOLD imaging o CT perfusion – contrast enhanced ``` o Nuclear medicine

Answer 141

o Transit time (MTT, or TTP) | o Cerebral blood volume (CBV)

Answer 142

``` Periventricular predominance Corpus callosum involvement Temporal lobe involvement Posterior fossa involvement U-fibre involvement Cortical involvement T1 black hole Cord lesions - but MR is relatively inconsistent for this ```

Answer 143

o Typical lesions are flame shaped | o Fired egg appearance in fresher lesions

Answer 144

Ovoid lesions perpendicular to the ventricles typical for MS and are the result of inflammation around penetrating venules

Answer 145

o Sagittal FLAIR and/or T2

Answer 146

o Not see in leukoaraisosis (Small vessel disease)

Answer 147

Cerebellar peduncle

Answer 148

o U fibres located right next to cortex, between grey matter and the white matter

Answer 149

o Hypointense lesions and indicates the chronic stage with white matter destruction, axonal loss and irreversible clinical outcome

Answer 150

- More likely to get large lesions | - More likely to get lesions affecting the basal ganglia/thalamus

Answer 151

- Can be demonstrated with iron oxide nanoparticles or Fluorine 19 rich nanoparticles on MR - Human studies have been undertaken - Can show macrophage recruitment - A negative contrast – loss of signal

Answer 152

 Posterior annulus  Facet joints  Para vertebral muscles  Anterior dura

Answer 153

 Tissue tension |  Chemical irritants

Answer 154

- Distortion in fascial attachments and muscles - Muscle fatigue causing local accumulation of metabolites - Stress in facet joint and Sacro iliac joint capsules - Inflammation of facet joints (OA) - Irritation of perivascular and periosteal nerves due to collapse, tumours, fractures and infection - Distortion of posterior annulus and PLL by discs

Answer 155

- Highest when sitting - Maximal at lowest end of spine - In healthy disc - end plate more likely to rupture than annulus under pressure

Answer 156

- Dehydration - Invasion of fibro cartilage by nucleus - Loss of elasticity - Fissuring - Uniform cartilage plate - Caused by decreased blood supply from the end plate

Answer 157

- In ageing disc dehydration and fissuring cause annulus to give way - Annulus rupture can occur in any direction by only symptomatic if posterior

Answer 158

Peak incidence of acute disc disease in early middle age | o High level of activity and early degenerative changes

Answer 159

Chronic disc disease Occurs later in life Disc flattening and dehydration

Answer 160

o OA of facet joints o Osteophytes o Ligamentous thickening o Deformity – spondylolisthesis

Answer 161

- 4,253 cadavers - 50-year olds o 69% of women and 80% of men - 70-year olds o 95% of men - Gross changes even in those with no complaints (Schmorl 1929)

Answer 162

o Nerve root o Common o Self-limiting o Not recurrent

Answer 163

``` o Spinal cord o Often stabilises o Some milder cases spontaneously improve o Not fully explained by compression  Vascular, congenital, ligamentous? ```

Answer 164

- Neck pain and stiffness - Headaches - Limb o Pain and paraesthesia o Sensory loss o Weakness o Reflex loss

Answer 165

- Slow onset or sudden with trauma - Upper limbs o Numb and clumsy o Muscle wasting - Lower limbs o Stiff heavy legs o Poor balance and falls

Answer 166

- Carpal tunnel syndrome - Ulnar nerve palsy - Thoracic outlet syndrome - Shoulder girdle problems - Brachial neuritis

Answer 167

``` X-ray o AP o Lateral o Oblique o Flexion-extension canal dimensions ``` MRI o Good resolution of soft tissue o High cord signal in T2 weighted image correlates to myelopathy and poor outcome CT/myelogram o Bony detail o Cord and roots seen EMG/NCS o To exclude double crush (compression at 2 more locations on a peripheral nerve) o E.g. nerve root and carpal tunnel

Answer 168

o Analgesia o Physiotherapy – avoid manipulation of the neck o Collar – for 4-6 weeks

Answer 169

o Decompress cord/roots and remove osteophytes | o Anterior/posterior approach depending on where compression is

Answer 170

o Radiculopathy – relieved in 80% | o Myelopathy – improved in 60% (complete resolution unlikely)

Answer 171

- Intractable pain - Progressive neurodefecit - Cord/root compression on imaging - Failure of conservative treatment

Answer 172

- Haemorrhage, infection, CSF leak - Recurrent laryngeal nerve damage - Tracheal, oesophageal damage - Carotid, vertebral artery damage - Root and cord damage – quadriplegic - Failed fusion - Painful hip wound and thigh - Bowel perforation

Answer 173

- Low back pain (50 to 90%) during their lifetime - 70% improve in 3 weeks - 90% in 2 months - 1% continue to have symptoms after 1 year - Peak incidence in 3rd and 4th decade of life - Nachemson’s review o 4.8% male, 2.5% female population beyond 35yrs experience sciatica

Answer 174

Smoking Pregnancy Certain professions

Answer 175

- Congenital o Meningeal cyst o Tethered cord syndrome o Conjoined nerve root - Acquired o Spinal stenosis o Spondylolisthesis o Juxtafacet cyst - Infectious o Discitis o Caries spine - Neoplastic o Spine/spinal cord tumours

Answer 176

- Plain radiography - MRI - CT scan - Myelography - EMG - Epidural venography - Discography

Answer 177

o Loss of lordotic curve o Scoliosis o Disc space narrowing o Main reason is to exclude other conditions

Answer 178

o Protect abnormal disc from strain | o Put the part at rest to encourage healing

Answer 179

- Decrease in general activity - Non-narcotic analgesics/NSAIDs - Muscle relaxant - Lumbosacral corset - Programme of back exercises

Answer 180

- Cauda equina syndrome with bladder and bowel deficit - Progressive motor deficit - Significant neurologic deficit with reduced straight leg raising - Failure of adequate conservative treatment - Recurrent episodes of sciatica

Answer 181

- Microdiscectomy - Fenestration - Hemilaminectomy - Decompressive laminectomy

Answer 182

- Nerve injury - CSF leak - Infections - Spinal instability - Post laminectomy kyphosis - Urinary retention - Injuries to great vessels/viscera - Chronic adhesive arachnoiditis - Spasm - Failed back surgery syndrome

Answer 183

o At 1 year 92% of surgical patients improved compared to 60% for non-surgical o However, at 4yrs and 5yrs no significant differences between the 2 groups with 60% improved

Answer 184

o Immediate surgical results better o At 6 months no difference between the groups o At 7 years patients who did not receive surgery had more episodes of lower back pain and sciatica and more lost time from work

Answer 185

Axons originating from anterior horn cells

Answer 186

- By cause - Acute vs chronic - Symmetrical vs asymmetrical (?multifocal) - Sensory vs motor vs mixed - Axonal vs demyelination - Large fibre vs small fibre

Answer 187

- Unknown – 30% - Endocrine diseases - Inflammatory diseases - Infective - Nutritional - Metabolic - Genetic - Neoplastic and paraneoplastic - Toxic and pharmacological agents

Answer 188

Diabetes | Hypothyroidism

Answer 189

``` Guillain-Barre syndrome SLE Sjogren's Vasculitis Sarcoidosis ```

Answer 190

Lyme disease Leprosy HIV

Answer 191

Vitamin B12, B1, vitamin E, B6 toxicity

Answer 192

Porphyria Copper deficiency Zinc toxicity

Answer 193

Charcot-Marie-Tooth disease Friedreich's ataxia Fabry disease

Answer 194

POEM disease MGUS SSCA

Answer 195

``` Vincristine Phenytoin Amiodarone Metronidazole Alcohol Statins ```

Answer 196

- Mononeuropathy - Mononeuropathy multiplex - Polyneuropathy

Answer 197

- Loss of appetite/Loss of weight - Rashes o Especially non-blanching - Skin discolouration - Diarrhoea - New autonomic features o Bladder dysfunction, erectile dysfunction, dry mouth and eyes, cardiac symptoms - Family history

Answer 198

- Small muscle wasting - Inverted champagne bottle wasting in legs - Hammer toes, high arched feet - Skeletal abnormalities – short fourth toe (Refsum’s disease) - Weakness – usually distal, but can be proximal as well (CIDP, GBS) - Reduced reflexes

Answer 199

- Angular stomatitis – B12, Folate - Glossitis – B12/Folate - Dentures/denture cream – Zinc toxicity - Mees lines – arsenic poisoning - Corkscrew hair – Menkes disease, Vitamin C deficiency - Burning/painful neuropathy – Amyloidosis, Alcohol - Orange tonsils – Tangiers disease - AIDS defining findings – HIV neuropathy

Answer 200

- FBC – indicates effects of vitamin deficiencies, alcohol, inflammation - ESR – Raised in inflammation, infection, neoplastic processes - RBC – Raised in DM - TFT – hypothyroidism - Serum immunoglobulin fixation – MGUS neuropathy, POEMS - B12 folate - EMG/NCS

Answer 201

Diabetic peripheral neuropathy - most common (75) o Diabetic autonomic neuropathy o Cranial neuropathy o Mononeuritis multiplex o Mononeuropathy o Treatment-induced neuropathy in diabetes (TIND)

Answer 202

- Symmetrical, length dependent sensorimotor - Attributable to metabolic and micro vessel alterations - Result of chronic hyperglycaemia exposure

Answer 203

o Pain management  Duloxetine and Pregabalin  Capsaicin/Lidocaine patches  Opiates – tramadol/codeine (ideally avoided) o Exercises – help improved nerve fibre regeneration o Diabetic foot management o Falls risk – 3 times more likely to fall

Answer 204

o Vasculitides o Connective tissue disorders o Granulomatous inflammation – Sarcoid o Diabetes

Answer 205

o Treatment should be as you treat renal involvement o Cyclophosphamide + IVMP o Non systemic – less aggressive – Management of the cause

Answer 206

o Slow, over many years o Length dependent o Motor or sensory o Sometimes very little symptoms but signs present

Answer 207

- Acute, subacute in onset - Rapidly progressive - Severe limitation in function - Length independent/asymmetrical - Multifocal - Motor predominant - Associated with dysautonomia - Demyelinating - Associated paraprotein/MGUS - Family history

Answer 208

up to 80 per 1000

Answer 209

- Neuropathy = disease of axons and myelin, long vulnerable to attack by ischaemia or autoimmunity - Neuronopathy = whole cell e.g. neurodegenerative, paraneoplastic

Answer 210

``` o Proprioception o Light touch, pressure vibration o Pain o Warm o Cold ```

Answer 211

``` o Weakness o Wasting o Fasciculation o Cramps o Neuropathic tremor o Cranial nerve manifestations e.g. double vision ```

Answer 212

o Bladder/bowel dysfunction o Blood pressure dysregulation o Syncope o Sexual dysfunction

Answer 213

o Carpal tunnel syndrome (Median nerve) o Ulnar neuropathy (entrapment at cubital tunnel) o Peroneal neuropathy (entrapment at the fibular head)

Answer 214

increased by systemic conditions e.g. hypothyroidism, pregnancy, acromegaly, HNPP

Answer 215

Idiopathic VII palsy Common, lifetime risk Can affect any age, gender Viral in some cases

Answer 216

``` o Exclude central cause o Steroids if presenting >72hrs o Treat underlying viral infection o Eye care o Surgery/Botox ```

Answer 217

Often compression/trauma | o Habitual leg crossing, fibular head fracture, knee surgery

Answer 218

- Complete or partial foot drop ± numbness

Answer 219

o Exclude L5 radiculopathy o Treat underlying cause o Physiotherapy o Splints

Answer 220

o Parasympathetic fibres on outside of nerve therefore more susceptible to compression o Autonomic involvement = blown pupil o Usually needs imaging

Answer 221

microangiopathic (HTN, T2DM)

Answer 222

berry aneurysm of posterior communicating artery (classic), basal skull fracture

Answer 223

- Usually not length dependent or symmetrical Progressive motor and sensory deficit Most commonly caused by vasculitis

Answer 224

- Length dependent o Longer fibres affected first - Initially sensory, but eventually sensorimotor - Most common type of neuropathy - Mostly talking about large fibre polyneuropathies - Small fibre – often idiopathic, investigations may be normal, occasionally autoimmune

Answer 225

A group of muscle diseases that result in increasing weakness and breakdown of skeletal muscles over time

Answer 226

- Loss of structural proteins - Defective enzymes - Disruption of sarcolemma-repair mechanisms - Loss of signalling molecules - Noncoding region mutations - Defective post translational modifications

Answer 227

- Over 30 inherited diseases - Causing progressive weakness and wasting of muscles - Replacement of muscle tissue with fibrous connective tissue - Cardiac involvement, respiratory involvement seen in some - CNS tissues not usually affected

Answer 228

Historical classification - e.g. Duchenne muscular dystrophy Clinical phenotype – e.g. facioscapulohumeral dystrophy, dystrophia myotonica Based on inheritance – AD, AR, X-linked Underlying genetic cause – e.g. DMD – dystrophinopathy

Answer 229

- X-linked recessive – Xp21

Answer 230

- Dystrophin localised at the sarcolemma – dystrophinopathy - Dystrophin links the ECM and cytoskeleton of each muscle fibre - Absence of dystrophin results not only reduced support in the muscle fibre but also results in excess calcium to penetrate sarcolemma o Due to alterations in calcium and signalling pathways – water enters mitochondria which burst o Results in a complex cascading process, oxidative stress within the cell damages the sarcolemma eventually causing cell death

Answer 231

o Large deletions, duplications, and point mutations that disrupt the reading frame cause of absence of dystrophin – DMD o BMD phenotype occurs when dystrophin is produced but abnormal – in frame deletions o Exceptions to reading frame rule – point mutations in binding areas BMD is milder than DMD as dystrophin is still present

Answer 232

``` o Usually presents with motor delayed milestones o Wheelchair by 13 years old o Cardiac involvement (100% after 18) o Respiratory involvement o Survival beyond 30 is unusual ```

Answer 233

o Later onset and ambulant into 20s o Worse cardiac involvement o Mean age of death – mid 40s

Answer 234

o Supportive – MDT approach to promote function and independence o Scoliosis corrective surgery as children o Manage cardiac failure and arrythmias – Beta blockers, ACEi, transplantation o NIV and cough assistance/physio o Steroids o Gene therapy – anti sense oligonucleotides weekly s/c injections o Family support o Female carriers

Answer 235

- DM1 – 1 in 7,400 | - DM2 – less common

Answer 236

- Most common genetic disease of muscle - Autosomal dominant DMPK (DM1) - Codes for myotonic dystrophy protein kinase  CTG repeats  Normally 5-37  DM1 – Over 50 repeats ZNF9 (DM2)  CCTG  Normally 10-33  DM2 - usually around 5000 repeats

Answer 237

o Disease onset younger and more severe in each generation | o CTG is unstable, growing by 200 per generation

Answer 238

Myotonia most common presentation o Pronounced after rest o Eases with warm up o Cranial, trunk and distal muscles

Answer 239

o Ptosis, wasting of temporalis, masseter, facial weakness o Tongue weakness o Long finger flexors and ankle dorsiflexors o Ocular motility can be affected o Diaphragm weakness, respiratory failure

Answer 240

o Cardiac dysrhythmia 2nd leading cause of death o Heart block, atrial tachycardias, ventricular tachycardia o Progressive conduction defects o Heart failure not uncommon – rare under 40, 30% at 70yrs o Prospective risk of sudden death 1.1% per year

Answer 241

o Sleep disturbance o Behavioural and cognitive change o White matter changes on MRI – cause uncertain

Answer 242

o Gall bladder problems o Intestinal dysmotility  Urgency  Diarrhoea  Constipation

Answer 243

o Thyroid, ovary, colon, endometrium, brain, eye

Answer 244

o Testicular atrophy o Reduced fertility o Erectile dysfunction

Answer 245

o Diabetes, insulin resistance o High cholesterol and triglycerides o Abnormal LFTs – no action unless other symptoms o Balding – men and women

Answer 246

Myotonia o Anticonvulsants, mexiletine Pain o Analgesic ladder Monitor o EEG, Glucose, lipids, cataracts, respiratory failure Erectile dysfunction Genetic counselling

Answer 247

- Prototypical disease of the neuromuscular junction - Antibody-mediated o Anti-acetylcholine receptor antibody identified and shown to pathogenic - Fatigable weakness

Answer 248

- Autoantibodies against acetylcholine receptors on post synaptic membrane o Produce complement mediated damage and increase the rate of AChR turnover - Leads to weakness and fatiguability of skeletal muscle - Thymus gland is involved in most patients - In a small proportion of patients who lack AChR antibodies, antibodies to muscle specific kinase (MuSK) or related proteins such as agrin can be found

Answer 249

- Antibodies present at site of pathology (i.e. the NMJ) - Antibodies from MG patients cause MG symptoms when injected into rodents - Immunisation of animals (i.e. with Ach) reproduces the disease - Therapies that remove antibodies ameliorate the disease

Answer 250

- UK – 15 per 100,000 - Europe – 4.5-10 per 100,000 - USA – 20 per 100,000 - Relatively rare - More females than males at young age o Although more men later in live o Biphasic and bimodal curve

Answer 251

o Ptosis o Diplopia o Pupil always spared o Must follow up to ensure it doesn’t progress to generalised MG

Answer 252

o Myasthenic crisis | o Cholinergic crisis

Answer 253

``` Clinical examination Antibody tests EMG CT thorax Tensilon test ```

Answer 254

Muscle fatigue

Answer 255

AChR - positive in 80% generalised, 50% ocular Anti-MuSK - in 7% No antibodies in 7% Thyroid - to rule out thyroid conditions

Answer 256

o Decrement – train of stimuli (electrophysiological fatigability) o Single fibre EMG – Jitter (95% sensitive)

Answer 257

o Look for thymoma (usually benign tumour)

Answer 258

Adminsitering edrophonium o AChE inhibitor o Can temporarily reverse MG signs o Administered IV and in a double-blind fashion o Not done anymore as can cause symptomatic bradycardia

Answer 259

o Increase the synaptic cleft acetylcholine concentration o Avoiding immune mediated end-plate damage o Removing antibodies and their production

Answer 260

Association of British Neurologist Guidelines 2015: (5) - Pyridostigmine + Prednisolone (if still symptomatic) acutely - Prednisolone at lowest effective dose to maintain remission - Alternative immunosuppression only introduced if there is failure to respond to prednisolone, or due to significant side effects

Answer 261

Anti cholinesterase inhibitor

Answer 262

Second line  Azathioprine – slow working  Mycophenolate  Methotrexate Third line  Cyclosporin  Rituximab

Answer 263

o Intravenous immunoglobulin o Maximise steroids o Plasma exchange o Ventilation

Answer 264

- Generally good but improvement takes months - Risk of iatrogenic side effects - 10% have brittle disease that can be very difficult to manage

Answer 265

- It’s a neuropathy - Acute (rare for a neuropathy) - Usually demyelinating (and potentially treatable) - Acute inflammatory demyelinating polyneuropathy

Answer 266

- ¬Acute ascending symmetric weakness hour to days, at its worst by 4 weeks - Pain in 2/3rds - LMN ± mild sensory signs - Facial weakness ± other CN signs in ½ - Respiratory weakness 1/3 - Bulbar involvement ½ - CVS instability 2/3 - (Sphincter signs) – rare in GBS but can happen

Answer 267

- First thing to become abnormal o Compared to NCS - CSF: Usually <5 WCC, protein <0.45 g/L, glucose >2/3rds blood concentration - In GBS – protein elevated but normal cells

Answer 268

- F wave first to become abnormal in an NCS | - Test of the conduction of the most proximal part of the nerve

Answer 269

- “Friendly fire” - T-cells mistakenly identify myelin epitopes as foreign “molecular mimicry” - Both cellular and humoral mechanisms - Interleukon-2 and TNF may be involved - Cytokine attract macrophages attack myelin - Complement-fixing anti-myelin antibodies are present - Ganglioside antibodies – attack axons

Answer 270

- What is it? o Clinical o Lumbar puncture o NCS after first week (can be normal, or delayed F waves) – can inform progress - What isn’t it? o Consider MRI to exclude acute cord lesion - What is complicating it? o Measure FVC o ECG - What’s the antibody? o Ganglioside antibodies (special circumstances)

Answer 271

A condition that is GBS but doesn't look like it - it presents atypically

Answer 272

- AMAN etc - Miller-fisher syndrome - Bickerstaff’s - Pharyngeal-cervical-brachial - Paraparetic

Answer 273

- Respiratory | - Cardiac

Answer 274

Intravenous immunoglobulin or plasmapheresis if unable to walk o Most people Best supportive care o Respiratory support in 1/3 o Arrhythmias o NG feeding Prevent/treat secondary complications o LMWH, infections, pain etc

Answer 275

Steroids ineffective | o (GBS steroid trial group. Lancet 1993)

Answer 276

- Most patients fully recover - >60% but can take up to 18 months - Death <5% - Residual disability - Poor prognostic factors – age, diarrhoea, weak arms (time to max disability?) - Recurrent GBS 2-5% - does this exist?

Answer 277

- Chronic inflammatory demyelinating neuropathy | - It’s demyelinating not axonal (potentially treatable)

Answer 278

- Like GBS but slower - Like GBS but relapses - Behaves more like a normal neuropathy - Not usually prodrome or the dramatic respiratory failure - LMN signs - LP high protein, NCS demyelination - Treatable with immunosuppressants

Answer 279

- Guillain-Barre syndrome progresses to nadir in <4weeks - CID progresses to nadir in >8 weeks - Between 4 and 8 weeks = Subacute inflammatory demyelinating polyneuropathy A spectrum?

Answer 280

- Slowly progressive – at least 8 weeks to nadir in 2/3 - Relapsing in 1/3 - Can present acutely - Symmetrical or asymmetrical - Gait problems - ICP headaches - LMN signs as in GBS - Large fibre sensory signs more frequent - Bulbar symptoms less frequent - Facial weakness and ophthalmoparesis can occur - Autonomic symptoms and respiratory weakness can occur - Can rarely be fatal - Many variants

Answer 281

- Similar to GBS - Look for alternative causes of demyelinating neuropathy o Paraproteins o Inherited o Drugs o HIV - NCS more useful - Antibodies can be useful in variants (e.g. anti-MAG) - Consider CMT genetics - Rarely nerve biopsy

Answer 282

- Evidence for steroids (Pred 60, or pulsed dex, van Schaik et al, Lancet neurol 2012) - Steroid-sparing agents may be used (azathioprine, mycophenolate, methotrexate, cyclophosphamide, cyclosporin) - IV immunoglobulin, PE

Answer 283

- Relapsing better than progressive? - 70% recover well from relapses - 90% respond to treatment initially, 70% sustained - Mortality - Chronic disease - Much is unknown

Answer 284

- Precise mechanism unknown - Cellular and humoral mechanisms - Perivascular inflammation with macrophages and lymphocytes - Evidence of chronic demyelination/remyelination on biopsies o Onion bulbs

Answer 285

- Based on 70 consecutive neurology cases - Systemically unwell (57%) - Headache (46%) - Stroke like episodes (41%) - Additional organ involvement (27%) - Mononeuropathy multiplex (17%) - Cranial nerve palsies (11%) - Seizures (11%) - Purely cognitive (5%) - Muscle involvement (3%)

Answer 286

- Headaches - Stroke like episodes/focal neurological deficit - Encephalopathic o Confusion, agitation, decreased level of consciousness - Foot drop/asymmetric neuropathy

Answer 287

- Based on 70 neurology cases - Isolated to CNS (26%) - Giant cell arteritis (23%) - Wegener’s spectrum (18%) - Associated with CTD (11%) - Isolated pachymeningitis (6%) - Churg Strauss (5%) - Isolated to PNS (3%) - PAN (2%) - Takayasu’s’ (2%)

Answer 288

- CNS infection o HSE, TB, viral encephalitis, HIV - CNS malignancy o Malignant meningitis, lymphomas - Venous sinus thrombosis - Subarachnoid haemorrhage/vasospasm - Embolic strokes due to SBE - Reversible cerebral vasoconstriction

Answer 289

- HIV, Varicella zoster, TB, syphilis, Hep C - In association with malignancies - In association with connective tissue diseases

Answer 290

- Raised inflammatory markers at baseline - ESR (80%) - CRP (70%) - Low albumin (57%) - High platelet count (46%) - But up to 20% - no abnormalities

Answer 291

- One or more abnormalities in <50% - Rheumatoid factor - P or C ANCA - Lots of patients have MGUS o Monoclonal gammopathy of underdetermined significance o Asymptomatic o Premalignant condition

Answer 292

- Abnormal in up to 80% of patients with CNS vasculitis - Raised protein most common (50%) - Lymphocytes (25%) - OCBs (20%) - Matched bands (25%) - Blood (15%)

Answer 293

- If the MRI scan is normal it is highly unlikely that the patient has CNS vasculitis o 100% sensitivity in biopsy proven cases - MRI usually normal in GCA at presentation - Imaging the arteries (MRA, CTA, 4 vessel angiogram) can be helpful but an abnormal result does not diagnose CNS vasculitis - DWI can be helpful in dating vasculitic strokes

Answer 294

- 18 patients with biopsy proven CNS vasculitis - All had abnormal MRI - Only 65% have abnormal angiograms (Pomper et al, AJNR, 1999) - In other series the sensitivity of angiograms was as low as 20% - Angiograms not helpful in small vessel vasculitis

Answer 295

- In patients with suspected primary angiitis of the CNS but with inconclusive imaging

Answer 296

- Sensitivity is somewhere between 53-74%, but can be increased to over 80% by targeting areas of imaging abnormalities - Not always positive but may reveal different underlying cause on further examination - Relatively safe and effective o (Beuker et al, Therapeutic advances in neurological disorders, 2018)

Answer 297

o Drugs e.g. cannabis, cocaine, amphetamines but also ergotamine, SSRI, IVIgs o Pregnancy and puerperium o Idiopathic

Answer 298

``` o Female predominance o Acute onset of headache (mimics SAH) o Usually no prodromal illness o Usually no focal neurology o Abnormal angiogram or CTA or MRA o Usually normal MRI but may have cortical SAH, intracerebral bleed, or CVA ```

Answer 299

67 consecutive cases of cerebral vasoconstriction syndrome over 3 years ``` o Spontaneous in 37% o Cannabis use in 32% o SSRI use in 21% o Postpartum in 12% o Cortical SAH in 22% o Intracerebral haemorrhage in 6% o Angiograms normal by 3 months (Brain, 2007) ```

Answer 300

- Some angiographic changes in vasculitis are permanent so not good for monitoring - May be useful in reversible cerebral vasoconstriction syndrome as by definition angiography becomes normal by 3 months (without any treatment) - MRI much more sensitive but beware of timing or MRI vs clinical state of patient

Answer 301

- Should be tailored to each case - Cyclophosphamide is not always essential - Adjust frequency of pulses according to patient’s clinical state - Avoid using steroids for too long - Mycophenolate seem the best choice for maintaining remission - Rituximab for resistant cases

Answer 302

- The little brain - The number of neurons in the cerebellum (100 billion) exceeds the total number in the remaining parts of the brain - Contains complete motor and sensory representation of the whole body - Controls the timing and pattern of motor activation during movement - Dysfunction causes ataxia (Greek for lack of order)

Answer 303

Purkinje cells are the only output

Answer 304

- Slurring of speech (staccato speech) - Oscillopsia (not very common) - Sensation that the surrounding environment is moving when it is not - Clumsiness (arms and legs) - Loss of precision of movement - Intention tremor - Unsteadiness when walking - Falls - Unsteadiness worse in the dark - Cognitive problems

Answer 305

- Gait ataxia - Truncal ataxia - Limb ataxia - Action tremor - Dysdiadochokinesia - Nystagmus - Dysarthria

Answer 306

- Congenital ataxias E.g. cerebellar dysgenesis - Diseases where ataxia is one of many features - Usually autosomal recessive disorders - Episodic ataxias (e.g. EA1, 2) - Autosomal recessive ataxias (e.g. FA) - Autosomal dominant ataxias (SCAs) - Sporadic ataxias (e.g. MSA-C, gluten ataxia)

Answer 307

Ataxias due to structural damage are not included in the classification

Answer 308

``` o Age of onset o Rate of progression o Additional features (genito-urinary, postural) o Pattern of involvement o Detailed family history o Alcohol intake o Exposure to drugs toxic to cerebellum ```

Answer 309

o Eye involvement (nystagmus, broken pursuit) o Limb ataxia o Gait ataxia o Symmetrical vs unilateral o Evidence of peripheral neuropathy or sensory o Neuronopathy (e.g. sensory ataxia) o Evidence of postural blood pressure fall

Answer 310

 Cerebrovascular damage (posterior circulation stroke)  Primary tumours  Secondary tumours  Hydrocephalus  MS (Primary progressive)  White matter involvement in leukodystrophy  Cerebellar dysgenesis/malformations

Answer 311

idiopathic sporadic ataxia Sheffield ataxia clinic 1996-2010, total of 640 patients assessed

Answer 312

- Most common – idiopathic sporadic ataxia - Gluten ataxia - Clinically probable MSA-C - Genetic diagnosis - Alcohol related - Paraneoplastic ataxia - Anti-GAD associated ataxia - Least common – opsoclonus myoclonus

Answer 313

A state of heightened immunological responsiveness to ingested gluten in genetically susceptible individuals (Marsh 1995)

Answer 314

No | Spectrum of mucosal damage ranges from normal to hypoplastic atrophic (Marsh Scanning Mricrosc, 1988)

Answer 315

- Ataxia most common - Peripheral neuropathy o Sensorimotor axonal neuropathy o Sensory ganglionopathy - Encephalopathy - Myoclonic ataxia (hyperexcitable brain) - Less common manifestations o Myopathy, myelopathy, epilepsy, chorea, migratory neuritis, stiff person syndrome

Answer 316

- Sporadic idiopathic ataxia but some familial cases described - Presence of serological markers of sensitivity to gluten

Answer 317

Based on antigliadin antibodies o 15% of all ataxias o 42% of all idiopathic sporadic ataxias o 12% of genetically characterised ataxias o 12% in healthy controls

Answer 318

Dietary treatment o Improvement of ataxia within a year of strict gluten free diet even in those patients without enteropathy o (Hadjivassiliou et al, J Neurol Neurosurg Psychiatry, 2003)

Answer 319

- Symmetrical sensorimotor length dependent neuropathy - Accounts for 26% of all neuropathies and 34% of idiopathic neuropathies - Neuropathy was found in 21% of patients with known coeliac disease on gluten free diet

Answer 320

o Neurophysiological evidence of improvement of the neuropathy within a year of adherence to a strict gluten free diet o Irrespective of the presence of enteropathy o (Hadjivassiliou et al, Dietary treatment of gluten neuropathy, Muscle and Nerve 2006)

Answer 321

- Episodic often severe and intractable headaches rarely with focal deficits - White matter abnormalities on MRI - Headache improves on gluten free diet; the white matter changes do not progress but do not resolve either

Answer 322

- Study on 33 consecutive patients with established CD - All patients underwent neurological examination and brain imaging - Abnormal cerebellar MR spectroscopy in over 50% - Significantly less cerebellar volume when compared to controls

Answer 323

- All patients underwent neurological examination followed by brain imaging - 100 consecutive patients - 61% had neurological symptoms o 45% headache, 26% balance, 14% sensory - 42% had evidence of neurological dysfunction on clinical examination o 38% evidence of cerebellar dysfunction including 9 with nystagmus, 5% sensory signs and 1 had myoclonus - Imaging o 44% had abnormal MR spectroscopy of the cerebellum (3% controls) o 56% of patients with abnormal MRs had clinical evidence of balance problems

Answer 324

- Patients presenting with neurological symptoms are likely to be diagnosed with CD much later (61 vs 47 years) - They are neurologically more severely affected at the time of presentation (clinical and imaging) - Diet has a stabilising effect, but they remain disabled if they had the ataxia for many years

Answer 325

Patients with the classical GI presentation have the advantage of early diagnosis and thus prevention of extraintestinal manifestations

Answer 326

Patients who benefit (GI or neurological symptoms) from a gluten free diet in the absence of enteropathy

Answer 327

- Only 41% of the neurology patients have enteropathy on biopsy - 37% no enteropathy but have the HLA DQ2 or DQ8 (potential CD) - 22% no enteropathy and HLA other than DQ2/DQ8 Distribution of ataxia in the 3 groups was similar

Answer 328

Transglutaminase 2

Answer 329

TG6 o 73% of patients with positive antigliadin antibodies and ataxia were also positive for TG6 o 40% of UK patients with newly diagnosed CD were positive for anti-TG6 but only 14% in a Finish cohort of patients with CD

Answer 330

o Provide sensory input about head velocity | o Enables vestibula-ocular (VOR) to generate eye movements that matches the velocity of the head movement

Answer 331

o Register forces related to linear acceleration o Utricle – horizontal translation with constant centre of gravity o Saccule – vertical translation with shifting centre of gravity

Answer 332

- Both generate the vestibulospinal reflex and the vestibulocollic reflex

Answer 333

o Processing of balance perception is a central process o Starts from the vestibular nerve o Is a complex interplay between the optical system, the proprioceptive system, the motor system and the cognitive centres

Answer 334

- Maintains posture | - Produces kinetic contractions to generate ocular stability and helps maintain muscle tone

Answer 335

- Distinguish between central and peripheral causes of imbalance - Formulation of effective management regimen including compensation, adaptation and habituation protocols with customised rehabilitation exercises - Particle repositioning manoeuvres - Exclusion/inclusion of vestibular pathology in solitary/multifactorial conditions

Answer 336

``` Different presentations Type - vertigo or otherwise Duration LOC Trigger Postural instability Visual vertigo ```

Answer 337

``` o Episodic o Sustained o Visual vertigo o Positional o Oscillopsia o Hearing o Central symptoms/ataxia o Headache o Postural instability ```

Answer 338

Vestibular pathology

Answer 339

Non-vestibular pathology

Answer 340

Movement, aural pressure changes and darkness induced

Answer 341

Triggered by movement from dependent position

Answer 342

Suggestive of migraine variant

Answer 343

Suggestive of TIA or central syndromes

Answer 344

``` o Nystagmus o Head impulse test o Provocation tests o Head shake test o Dynamic visual acuity ```

Answer 345

o Non-vestibular nystagmus o Pursuits and saccades o VOR cancel

Answer 346

o Head heave test o Subjective visual vertical o Ocular counter rolling o Skew deviation

Answer 347

``` o Romberg tests o Unterberger and Fukuda – Stepping on spot with eyes closed o Quix and Barany tests o Gait tests o Lateral flexion ```

Answer 348

- Usually horizontal with fast and a quick phase - May have a latent period - Sustained by does not change direction on gaze eccentricities and may fatigue after some time - Follows Alexander’s law o Nystagmus is increased with the eyes directed to the fast phase direction o E.g. down in a downbeat nystagmus - Abolished or decreased by optic fixation - Does not rebound on spontaneous gaze - Any nystagmus or eye movement which does not follow the above may be central

Answer 349

- Pure Tone Audiometry (PTA), Tympanometry and Otoacoustic Emissions (OAE) o To assess the function of the ear - Quantification of vestibular hypofunction – Videonystagmography o Nystagmus o Dix Hallpike test – to exclude BPPV o Caloric tests – tests function of lateral semi-circular canals o Smooth pursuit and saccades - Rotatory chair tests and video head impulse test (vHIT) - Dynamic posturography for assessing central sensory organisation o Also useful for prognosis - Subjective visual vertical and Visual evoked myogenic potential (VEMP) o Assesses otolith function - Imaging studies – CT, MRI, Doppler - Blood tests when indicated

Answer 350

- Poor eye/head stabilisation - Inadequate/inappropriate CNS activity - Psychological dysfunction/age - Medicines/illness - Inadequate/impaired musculoskeletal activity - Impaired/inappropriate CNS balance strategies - Impaired sensory inputs - Fluctuating vestibular activity - Disordered perception of stability

Answer 351

- 17% at all ages, 40% from 60yrs - 26% are disabled - 40% are otological - 33% of falls due to peripheral vestibular problem

Answer 352

- Acute vestibular event o Infection or vascular - Intermittent decompensation following acute event o Traumatic fibrosis, tumour, space occupying lesion - Paroxysmal irritation of the vestibular system o BPPV, endolymphatic hydrops, vestibular paroxysmia, cervical causes - Mal De Debarquement (MDD) like syndrome and visual vertigo - Bilateral vestibular failure

Answer 353

- Inflammation - Trauma - Infection - Tumour - Idiopathic - Degeneration - Ototoxic - Others – e.g. hyperviscosity, anaemia, metabolic

Answer 354

- Benign paroxysmal positioning vertigo (18.3%) - Phobic postural vertigo (PPV) (15.9%) - Vestibular migraine (9.6%) - Vestibular neuritis (7.9%) - Meniere’s disease (7.8%) - Bilateral vestibulopathy (3.6%) - Psychogenic vertigo (3.6%) - Vestibular paroxysmia (2.9%)

Answer 355

infection, inflammatory, vascular or SOL – sudden onset lasting for days followed by intermittent and episodic if decompensated o Includes neuritis, labyrinthitis and TIA

Answer 356

Sudden onset, intermittent, positional lasting few seconds, recurrent and 7 types

Answer 357

sudden onset lasting for minutes to days, fluctuating with audiological features

Answer 358

sudden and pole axing lasting for few seconds, due to vestibular neuralgia as a result of compression in cerebellar pontine angle

Answer 359

migrainous features with dizziness lasting for minutes to hours with other autonomic features

Answer 360

sensation of rocking after travel, possible otolith related

Answer 361

- Chronic non episodic dizziness as difficult decompensation - Alleviated on eye closure - Neurological signs and central derangements of VOR control - Ataxia or movement disorders including tremors - May show signs of peripheral vestibular insufficiency in AICA infarction - Diagnosis by imaging and specific blood markers if indicated - Treatment of cause and physiotherapy o Vestibular physiotherapy effective in 30%

Answer 362

- With or without overt vestibular or central illness - Associated with somatisation - Continuous feeling of dizziness - Includes phobic postural vertigo and anxiety related vertigo - Treated by management of psychiatric condition if any, stress and relaxation exercises and CBT

Answer 363

- Treatment of active or acute condition with anti-labyrinthine medication or anti migraine therapy - Carbamazepine for vestibular neuralgia - Customised vestibular and frequency and site-specific rehabilitation - Particle repositioning for BPPV - Treatment for cause for decompensation - Surgery for space occupying lesions, vestibular paroxysmia - Stress management and CBT

Answer 364

- Paucity of dedicated vestibular services with limited access to integrated MDT - Referrals primarily directed to specialities with general training in vestibular sciences - Unavailability of dedicated medical expertise to patients presenting in a general service - An average of 4.5 physician visits per patient before receiving correct diagnosis - Cost of delay is significant – circa £2000 per patient - (Data from RCP London)